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Drug-Target Interaction

Drug

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PubChem ID:73094
Structure:
Synonyms:
(-)-1-Chloro-3-tosylamido-7-amino-2-heptanone
2364-87-6
4238-41-9
AC1L2J9B
AIDS-042745
AIDS042745
alpha-Tosyl-L-lysylchloromethyl ketone
AR-1K3052
Benzenesulfonamide, N-((1S)-5-amino-1-(chloroacetyl)pentyl)-4-methyl-
Benzenesulfonamide, N-(5-amino-1-(chloroacetyl)pentyl)-4-methyl-, (S)-
BRN 2885388
C00896
CCG-205254
CHEMBL466465
CK004
DB08603
Lopac-T-7254
Lopac0_001180
LS-154095
N-alpha-p-Tosyl-L-lysine chloromethyl ketone
N-alpha-Tosyl-L-lysyl-chloromethylketone
n-[(3s)-7-amino-1-chloro-2-oxoheptan-3-yl]-4-methylbenzenesulfonamide
N.alpha.-pTosyl-L-lysine chloromethylketone
Na-p-Tosyl-L-lysine chloromethyl ketone hydrochloride
NCGC00016045-01
NCGC00162359-01
NCGC00162359-02
p-Toluenesulfonamide, N-(5-amino-1-(chloroacetyl)pentyl)-, L-
TLCK
Tos-Lys-CH2Cl
Tosyl-K-CMK
Tosyl-L-lysine chloromethyl ketone
Tosyl-Lys-CMK
Tosyllysine chloromethyl ketone
Tosyllysyl chloromethyl ketone

Target

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Uniprot ID:ICE_DROME
Synonyms:
Caspase
drICE
EC-Numbers:3.4.22.-
Organism:Drosophila melanogaster
Fruit fly
PDB IDs:-

Binding Affinities:

Ki: Kd:Ic 50:Ec50/Ic50:
----

References:

11746380
Involvement of TLCK-sensitive serine protease in colchicine-induced cell death of sympathetic neurons in culture.. C Mitsui; K Sakai; T Ninomiya; T Koike (2001) Journal of neuroscience research display abstract
Superior cervical ganglion (SCG) cells from neonatal rats underwent apoptosis upon treatment with colchicine, a microtubule-disrupting agent. Western blotting and activity measurements showed that caspase-3 was indeed activated, but its peptide inhibitor (Ac-DEVD-CHO) neither suppressed nuclear fragmentation nor rescued the neurons from cell death. z-VAD-fmk, the general inhibitor of caspases, prevented nuclear fragmentation and delayed the cell death. Moreover, N-alpha-tosyl-L-lysine chloromethyl ketone (TLCK), but not N-alpha-tosyl-L-phenylalanine chloromethyl ketone (TPCK), prevented nuclear fragmentation and provided neuronal protection as well. The combination of both z-VAD-fmk and TLCK provided a long-term neuronal protection (>4 days), whereas neither one alone could do so, suggesting that there are both caspase-dependent and -independent pathways. TLCK-sensitive serine protease is also likely to act upstream of caspase-3 in a caspase-dependent pathway. Electron microscopic observations demonstrated that z-VAD-fmk suppressed nuclear fragmentation and improved mitochondrial swelling, but failed to prevent vesicular formation, which resulted in a slowly-occurring necrosis. More importantly, TLCK effectively blocked this abundant vesicular formation along with suppressing chromatin condensation. Thus, the combination of both conferred a nearly normal morphology, which is consistent with the results of cell survival experiments. These findings clearly indicate that TLCK-sensitive serine protease plays multiple roles in caspase-dependent and -independent pathways of colchicine-induced cell death, and suggest a novel mechanism underlying a necrotic pathway involving ER swelling and vesicular formation.